EP2455363B1 - Method for manufacturing spilanthol and intermediate manufacturing product therefor - Google Patents

Method for manufacturing spilanthol and intermediate manufacturing product therefor Download PDF

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Publication number
EP2455363B1
EP2455363B1 EP10799865.0A EP10799865A EP2455363B1 EP 2455363 B1 EP2455363 B1 EP 2455363B1 EP 10799865 A EP10799865 A EP 10799865A EP 2455363 B1 EP2455363 B1 EP 2455363B1
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EP
European Patent Office
Prior art keywords
group
isobutyl
spilanthol
mol
carbon atoms
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Not-in-force
Application number
EP10799865.0A
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German (de)
English (en)
French (fr)
Other versions
EP2455363A4 (en
EP2455363A1 (en
Inventor
Shigeru Tanaka
Kenya Ishida
Kenji Yagi
Hideo Ujihara
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Takasago International Corp
Original Assignee
Takasago International Corp
Takasago Perfumery Industry Co
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Publication of EP2455363A4 publication Critical patent/EP2455363A4/en
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Publication of EP2455363B1 publication Critical patent/EP2455363B1/en
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
    • A23L2/52—Adding ingredients
    • A23L2/56—Flavouring or bittering agents
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/20—Synthetic spices, flavouring agents or condiments
    • A23L27/202—Aliphatic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/42—Amides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q13/00—Formulations or additives for perfume preparations
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/02—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
    • C07C233/09—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to carbon atoms of an acyclic unsaturated carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and unsaturated
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
    • C11B9/00—Essential oils; Perfumes
    • C11B9/0007—Aliphatic compounds

Definitions

  • the present invention relates to an amide ester enabling manufacturing spilanthol which is useful as flavor and fragrance in an aromatically favorable state.
  • Spilanthol N-isobutyl-2,6,8-decatrienamide
  • a (2E, 6Z, 8E) isomer is known to be a main component of Spilanthes oleracea, and as an effective component having strong numbing and astringent actions.
  • the (2E, 6Z, 8E) isomer is useful as a sense stimulus component in a wide range of products such as foods, beverages, fragrances and cosmetic.
  • Patent Literature 1 discloses several industrially-applicable production methods.
  • Patent Literature 1 WO2009/091040 Al
  • An object of the present invention is to provide a method for manufacturing aromatically favorable spilanthol in high yield, and a novel intermediate used in the method.
  • the present inventors have earnestly studied to achieve the above-described object. As a result, the inventors have found out that by using a novel amide ester as an intermediate, high-purity, aromatically favorable spilanthol is obtained in high yield.
  • the present invention includes the following contents.
  • a food, beverage, fragrance, cosmetic, or pharmaceutical including 2,6,8-decatrienamide synthesized by the method mentioned in the paragraph above and having a chemical purity of 80% or more and a content of a 2E,6Z,8E-isomer of 65% or more.
  • the present invention provides a novel intermediate useful in manufacturing N-isobutyl-2,6,8-decatrienamide (spilanthol) useful as flavors and fragrances.
  • the use of the intermediate enables manufacturing of high-purity, aromatically favorable spilanthol in high yield.
  • a compound of the present invention represented by a general formula (1) is an amide ester which can be obtained by the following method.
  • Examples of an alkyl group having 1 to 6 carbon atoms represented by R 1 include a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a s-butyl group, a t-butyl group, a n-pentyl group, a n-hexyl group, and the like.
  • R 1 represents a phenyl group which may be substituted with an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, or a halogen atom.
  • alkyl group include a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a s-butyl group, and a t-butyl group.
  • alkoxy group having 1 to 4 carbon atoms examples include a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group, an isobutoxy group, a s-butoxy group, and a t-butoxy group.
  • halogen atom examples include a fluorine atom, a chlorine atom, and a bromine atom.
  • R 1 is preferably an alkyl group having 1 to 4 carbon atoms. Above all, a methyl group is more preferable.
  • Examples of a hydrocarbon group having 1 to 8 carbon atoms represented by R 2 include: linear or branched alkyl groups such as a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a s-butyl group, a t-butyl group, a pentyl group, a 2-methylbutyl group, and a hexyl group; a phenyl group and alkyl-substituted phenyl groups such as a tolyl group and a xylyl group; and aralkyl groups such as a benzyl group and a phenethyl group.
  • R 2 is preferably an isobutyl group or a s-butyl group.
  • Examples of an acylating agent used herein include acid anhydrides (R 1 COOCOR 1 ), acid chlorides (R 1 COCl), and the like.
  • R 1 include those described above.
  • Specific examples of the acid anhydride include acetic anhydride, propanoic anhydride, butyric anhydride, and the like.
  • Examples of the acid chloride include acetyl chloride, propionyl chloride, pivaloyl chloride, benzoyl chloride, and the like.
  • a basic compound coexists.
  • the basic compound used include triethylamine, tributylamine, pyridine, sodium carbonate, sodium hydroxide, potassium hydroxide, and the like. Among these, triethylamine is preferable.
  • the acylation reaction for the compound (h) can be performed at a temperature of approximately -5°C to 100°C, preferably 10°C to 30°C. The reaction period of around approximately 1 hour to 6 hours is sufficient.
  • a solvent which can be used in the reaction include toluene, hexane, heptane, diethyl ether, and tetrahydrofuran. Among these, toluene is preferable.
  • the amount of the acylating agent used is 1 time to 2 times, preferably 1.05 times to 1.2 times, as large as the compound (h) in terms of mole.
  • the product can be purified by extraction, distillation, various chromatographies, or the like.
  • the compound (h) which is the raw material of the amide ester of the compound of the present invention can be produced, for example, by the following method. (where each wavy line represents a cis configuration, a trans configuration, or a mixture of the two configurations).
  • Examples of a basic compound used herein include amines, alkyllithiums, Grignard reagents, metal hydrides, metal amides, metal alcoholates, and the like.
  • Specific examples of the basic compound include triethylamine, pyridine, 1,8-diazabicyclo[5.4.0]-7-undecene, n-butyllithium, t-butylmagnesium chloride, sodium hydride, lithium amides, lithium diisopropylamide, sodium methoxide, sodium t-butoxide, potassium t-butoxide, and the like.
  • Preferable examples of the basic compound include sodium t-butoxide and potassium t-butoxide.
  • the reaction can be performed at a temperature of approximately -20°C to 50°C, preferably 5°C to 10°C.
  • the reaction period of around approximately 1 hour to 5 hours is sufficient.
  • a solvent which can be used in the reaction include toluene, heptane, and tetrahydrofuran. Among these, toluene is preferable.
  • the amount of the basic compound used is 1 time to 2 times, preferably 1.05 times to 1.2 times, as large as the compound (1) -i-Bu in terms of moles.
  • the product can be purified by extraction, distillation, various chromatographies, or the like.
  • the spilanthol obtained in this manner is useful as a flavor additive in foods, beverages, fragrances, cosmetics, pharmaceuticals, and the like, by itself or in combination with sense (the sense of taste, skin sensation, and the like) stimulants such as existing cooling or warming agent, and the like, and more specifically useful as an effective component providing or enhancing cooling sensation, warming sensation, alcohol sensation, carbonation sensation, saliva secretion effect, or the like.
  • Examples of the above-described existing cooling agent include menthol, menthone, camphor, pulegol, isopulegol, cineol, mentha oil, peppermint oil, spearmint oil, eucalyptus oil, 1-methoxypropane-1,2-diol, N-alkyl-p-menthane-3-carboxamide, N-[(4-cyanomethyl)phenyl]-p-menthanecarboxamide, 3-1-menthoxy-2-methylpropane-1,2-diol, p-menthane-3,8-diol, 2-1-menthoxyethane-1-ol, 3-1-menthoxypropane-1-ol, 1-menthyl lactate, menthone glycerol ketal, N-methyl-2,2-isopropylmethyl-3-methylbutanamide, menthyl glyoxylate, monomenthyl glutarate, monomenthyl succinate, dimenthyl glutarate
  • examples of the warming (hot taste) agent include vanillyl ethyl ether, vanillyl propyl ether, vanillyl butyl ether, vanillin propylene glycol acetal, ethyl vanillin propylene glycol acetal, capsaicin, gingerol, red pepper oil, red pepper oleoresin, ginger oleoresin, nonylic acid vanillylamide, jambu oleoresin, Japanese pepper extract, sanshool-I, sanshool-II, sanshoamide, piper nigrum extract, chavicine, piperine, and the like. These can be used alone or by optionally blending two or more of them.
  • spilanthol may be directly blended in various products such as foods, beverages, fragrances, cosmetics, and pharmaceuticals. Particularly, it is possible to first blend spilanthol in a flavor or fragrance composition together with the sense stimulant described above, and then blend this flavor or fragrance composition in a product.
  • the foods and beverages include drinks such as fruit drinks, fruit wines, milk drinks, carbonated drinks, soft drinks and drink preparations; frozen desserts such as ice creams, sherbets and ice candies; desserts such as jelly and pudding; Western-style confections such as cake, cookie, chocolate and chewing gum; Japanese-style confections such as bean jam bun, sweet beans jelly and uiro; jams; candies; breads; tea drinks or luxury drinks such as green tea, Oolong tea, black tea, persimmon leaf tea, chamomile tea, striped bamboo tea, mulberry tea, Houttuynia cordata tea, Pu-erh tea, Mate tea, Rooibos tea, Gymnema tea, guava tea, coffee and cocoa; soups such as Japanese style soup, Western style soup and Chinese soup; flavor seasonings; various instant drinks and foods; various snack foods; and the like.
  • drinks such as fruit drinks, fruit wines, milk drinks, carbonated drinks, soft drinks and drink preparations
  • frozen desserts such
  • fragrances and cosmetics include fragrance products such as eau de perfume, eau de toilette and eau de Cologne; basic skin cares such as face washing cream, cleansing cream, cold cream, massage cream, milky lotion, skin toner, beauty lotion, pack and make remover; finishing cosmetics such as foundation, loose face powder, pressed face powder, talcum powder, lipstick, lip cream, rouge, eye liner, mascara, eye shadow and eye pack; hair cosmetics such as pomade, set lotion, hair oil, hair treatment, hair cream, hair tonic, hair liquid, hair spray, revitalizing hair tonic and hair dye; medicinal cosmetics such as suntan cosmetic, antiperspirant, after shaving lotion and jell, permanent wave preparation, medicinal soap, medicinal shampoo and medicinal skin cosmetic; hair care products such as shampoo, rinse, rinse in shampoo, conditioner, treatment and hair pack; body cleaners such as soap, body soap, body shampoo and hand soap; bathing preparations such as bath preparation (bath salt, bath tablet, bath liquid, and the like), foam bath (bubble bath and the like), bath oil (bath perfume,
  • Examples of the pharmaceuticals include skin external preparations such as poultice preparations and ointments, troches, oral medicines, and the like.
  • the amount of the spilanthol to be added to and blended in various foods, beverages, fragrances, cosmetics, and pharmaceuticals greatly varies depending on a target or the like, but preferably is 0.00001 to 30% by mass, more preferably 0.0001 to 10% by mass, based on a normal target.
  • the phosphonium salt (b) (420 g, 0.92 mol), toluene (1600 ml), potassium carbonate (506.2 g, 3.66 mol), and crotonaldehyde (256.7 g, 3.66 mol) were put into a 5-L flask, followed by stirring at 65°C for 7 hours.
  • the reaction solution was cooled to room temperature, and water (840 g) was put thereinto, followed by stirring for 30 minutes, and then subjected to separation of liquid.
  • the solvent was evaporated from the organic layer under a reduced pressure. A solid thus precipitated was removed by filtration. This solution was distilled under a reduced pressure (65 to 70°C/2 mbar (1.5 torr)), and ethyl 4,6-octadienoate (c) was obtained (114.4 g, yield 74%).
  • magnesium chloride (75.3 g, 0.79 mol), THF (560 ml), and a methyl malonate monopotassium salt (155 g, 0.996 mol) were put into another prepared 2-L flask.
  • the above-described reaction solution was added dropwise thereinto for 1 hour, followed by further stirring for 5 hours.
  • a 35% aqueous solution of hydrochloric acid (265 g, 2.55 mol) was added dropwise thereinto, followed by separation of liquid.
  • the organic layer was washed twice with a 10% aqueous solution of sodium carbonate (660 mL) .
  • Methyl 3-hydroxy-6,8-decadienoate (g) (86.1 g, 0.43 mol) and isobutylamine (95.3 g, 1.3 mol) were put into a 500-ml flask, followed by stirring at 90°C for 24 hours. After isobutylamine was recovered under a reduced pressure, heptane (700 ml) was added thereto, followed by cooling to 0°C. A white solid thus precipitated was filtered and dried under a reduced pressure. Thus, N-isobutyl-3-hydroxy-6,8-decadienamide (h) was obtained (85.2 g, 0.35 mol, yield 82%).
  • N-isobutyl-3-hydroxy-6,8-decadienamide (h) (80.0 g, 0.336 mol), toluene (240 ml), triethylamine (39.65 g, 0.403 mol), and DMAP (0.21 g, 0.0017 mol) were put into a 500-ml flask. While the reaction temperature was being adjusted to 20°C, acetic anhydride (37.7 g, 0.370 mol) was added dropwise for 1 hour. After stirring for 3 hours, water (160 ml) was added thereto, and the organic layer was separated.
  • t-BuONa 35.03 g, 0.361 mol
  • toluene 600 ml
  • N-isobutyl-3-acetoxy-6,8-decatrienamide 93.0 g, 0.331 mol
  • Water 200 ml was added thereto, and the organic layer was separated. Then, washing with water (186 mL) was carried out four times, and the solvent was removed under a reduced pressure.
  • N-isobutyl-2,6,8-decatrienamide (spilanthol) was synthesized by removing the methanesulfonate moiety. The stability and sensory evaluation thereof were compared with those of N-isobutyl-2,6,8-decatrienamide (spilanthol) obtained in Reference Example 2 above.
  • N-isobutyl-3-hydroxy-6,8-decadienamide (h) (85.2 g, 0.35 mol), ethyl acetate (680 ml), and triethylamine (72.1 g, 0.70 mol) were put into a 1-L flask equipped with a stirrer, a thermometer, and a dropping funnel, followed by cooling to 5°C. Then, methanesulfonyl chloride (44.7 g, 0.392 mol) was added dropwise thereto for 1 hour. After completion of the dropwise addition, water (170 ml) was added thereto, followed by separation of liquid.
  • N-isobutyl-3-sulfonyloxy-6,8-decadienamide (i) was obtained (108.9 g, yield 98%).
  • N-isobutyl-2,6,8-decatrienamide obtained in Comparative Example 1 hardly had an unusual odor and exhibited excellent numbing and astringent actions.
  • the present invention provides a novel intermediate useful in manufacturing N-isobutyl-2,6,8-decatrienamide (spilanthol) useful as flavors and fragrances.
  • the use of the intermediate enables manufacturing of high-purity spilanthol in high yield, the spilanthol being also favorable in terms of thermal stability, odor, and effectiveness.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
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  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Polymers & Plastics (AREA)
  • Food Science & Technology (AREA)
  • Nutrition Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Wood Science & Technology (AREA)
  • Birds (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Dermatology (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Cosmetics (AREA)
  • Seasonings (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Fats And Perfumes (AREA)
EP10799865.0A 2009-07-14 2010-07-14 Method for manufacturing spilanthol and intermediate manufacturing product therefor Not-in-force EP2455363B1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2009165530 2009-07-14
PCT/JP2010/061912 WO2011007807A1 (ja) 2009-07-14 2010-07-14 スピラントールの製造法及びその製造中間体

Publications (3)

Publication Number Publication Date
EP2455363A1 EP2455363A1 (en) 2012-05-23
EP2455363A4 EP2455363A4 (en) 2012-12-26
EP2455363B1 true EP2455363B1 (en) 2014-10-01

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EP10799865.0A Not-in-force EP2455363B1 (en) 2009-07-14 2010-07-14 Method for manufacturing spilanthol and intermediate manufacturing product therefor

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US (1) US9029593B2 (zh)
EP (1) EP2455363B1 (zh)
JP (1) JP5587313B2 (zh)
CN (1) CN102471238B (zh)
ES (1) ES2512240T3 (zh)
IN (1) IN2012DN00361A (zh)
WO (1) WO2011007807A1 (zh)

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FR2986001B1 (fr) 2012-01-24 2014-08-15 Robertet Sa Nouveau procede de concentration de spilanthol et/ou de ses isomeres et/ou homologues
WO2013140973A1 (ja) * 2012-03-23 2013-09-26 大正製薬株式会社 飲料
WO2016031292A1 (ja) * 2014-08-29 2016-03-03 三栄源エフ・エフ・アイ株式会社 経口組成物用添加剤
BR102016017871B1 (pt) * 2016-07-29 2023-03-21 Universidade Estadual De Campinas - Unicamp Processo de obtenção do espilantol e análogos, espilantol e análogos obtidos

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JPH0790294A (ja) 1993-09-20 1995-04-04 Lion Corp スピラントール高含有精油及びその製造方法並びにスピラントール高含有精油配合口腔用組成物
WO2004110439A1 (en) * 2003-06-13 2004-12-23 Ecopia Biosciences Inc. Polyene oxazoles with antitumour activity and processes for their preparation using a streptomyces strain
FR2865131B1 (fr) * 2004-01-15 2007-08-24 Gattefosse Ets Sa Utilisation d'un extrait d'acmella oleracea pour son effet botox like dans une composition cosmetique anti-rides
JP4679132B2 (ja) 2004-12-20 2011-04-27 小川香料株式会社 炭酸飲料用添加剤
JP4688517B2 (ja) 2005-02-15 2011-05-25 小川香料株式会社 高甘味度甘味料の呈味改善剤
JP4530906B2 (ja) * 2005-04-25 2010-08-25 小川香料株式会社 飲食品の香味増強剤
JP4508932B2 (ja) 2005-04-25 2010-07-21 小川香料株式会社 呈味増強剤及び該呈味増強剤を含有する香味料並びに該香味料を含有する飲食物
EP2058297B1 (de) * 2007-11-08 2015-05-20 Symrise AG Verwendung von Alkamiden zur Maskierung eines unangenehmen Geschmacks
JP5401708B2 (ja) * 2008-01-18 2014-01-29 高砂香料工業株式会社 （２ｅ，６ｚ，８ｅ）−ｎ−イソブチル−２，６，８−デカトリエナミド（スピラントール）の製造方法

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US20120116116A1 (en) 2012-05-10
EP2455363A4 (en) 2012-12-26
CN102471238B (zh) 2014-04-02
ES2512240T3 (es) 2014-10-23
CN102471238A (zh) 2012-05-23
IN2012DN00361A (zh) 2015-05-22
JP5587313B2 (ja) 2014-09-10
US9029593B2 (en) 2015-05-12
WO2011007807A1 (ja) 2011-01-20
JPWO2011007807A1 (ja) 2012-12-27
EP2455363A1 (en) 2012-05-23

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